tbuckley/cabot-search huggingface dataset:
Results of digital patient-reported outcomes measures (PROMs) data collection for patients with localized prostate cancer at diagnosis.
Authors: Sophie Knipper, Karel Dewulf, Nicolas Branger, Stanislas Rybikowski, Thomas Maubon, Naji Salem, Mathilde Guerin, Cecile Vicier, Gwenaelle Gravis, Jochen Walz, Geraldine Pignot
Journal: Journal of Clinical Oncology (2023)

e17103 Background: Patient-reported outcomes measures (PROMs) allow optimal evaluation of side effects of treatments and their impact on quality of life. Therefore, the objective of our study was to analyze the functional outcomes at different timepoints for urinary continence and erectile function in patients treated with active surveillance (AS), brachytherapy (BT), radiotherapy (RT, +/- hormonal treatment (HT)) and radical prostatectomy (RP). Methods: Since May 2019, all patients treated for localized prostate cancer in our center have been offered inclusion in a digital prospective program, with automated sending of PROMs questionnaires via a dedicated digital application, before treatment (baseline), at 1 (M1), 3 (M3), 6 (M6) and 12 months (M12). Data were analyzed for urinary continence and erectile function (EPIC-26 HRQOL Domain Summary Score of Urinary Incontinence (UI) and Sexuality) according to treatment strategy. Results: Overall, 552 patients answered questionnaires (05/2019-12/2022), including 97 AS patients, 23 patients treated by BT, 9 patients treated by RT, 37 patients treated by RT with HT and 386 patients treated by RP. Regarding continence, the median UI score at M12 (compared to baseline) was 88 (vs. 100) for AS, 100 (vs. 100) for BT, 100 (vs. 100) for RT, 93 (vs. 100) for RT with HT and 100 (vs. 100) for RP. Regarding erectile function, the median sexuality score at M12 (compared to baseline) was 100 (vs. 73) for AS, 40 (vs. 61) for BT, 40 (vs. 47) for RT, 17 (vs. 54) for RT with HT, 32 (vs. 67) for RP. Conclusions: Surgical treatment transiently affects continence but with almost complete recovery at one year in the majority of cases. However, erectile dysfunction remains a critical issue with an important deterioration for surgery as well as radiotherapy with combined HT. [Table: see text]
Disparities in molecular tumor board recommendations and treatment implementation.
Authors: Jack McNamara Hensien, Chiara Pierattini, Sanja Karovic, Erik Dvergsten, Jamie Randall, Timothy Lewis Cannon, Arthur Winer, Raymond Couric Wadlow
Journal: Journal of Clinical Oncology (2023)

e18582 Background: The Inova Schar Cancer Institute Molecular Tumor Board (ISCI MTB) is a multi-disciplinary group that meets biweekly to discuss molecular test results for patients with advanced cancer to inform potential targeted therapy and clinical trial options. Previous work analyzing the racial distribution of patients in the ISCI MTB compared to the institutional cancer registry (CR) demonstrated that self-identified Black/African American patients were under-represented in the MTB. We next sought to evaluate the association between race and the implementation of MTB-recommended therapy. Methods: We evaluated ISCI MTB records from 1/1/16 to 12/31/21 and identified patients with at least one treatment recommendation informed by molecular biomarker results, including clinical trials, targeted medications, immunotherapy, and chemotherapy. Patient data were extracted from the EMR using the Epic Slicer/Dicer Tool and integrated with the MTB REDCap database. Manual chart review was used to fill missing data and identify patients for whom at least one MTB recommendation was implemented. Recommendation implementation was defined as treatment with or prescription of a recommended therapy or evaluation for a clinical trial. Results: 244 of 530 patients (46%) had one or more MTB recommendations implemented. There was no clear distinction in age at MTB presentation (64 vs 65) or sex (45% of males and 47% of females vs 55% of males and 53% of females) between patients who had recommendations implemented and those who did not. 45% of White/Caucasian, 41% of Asian, 56% of Black/African American, and 58% of Hispanic/Latino patients had MTB recommendations implemented. No statistically significant differences in implementation of recommendations were observed for age, sex, or race. Conclusions: Fewer than half of patients with advanced cancer receive biomarker-directed or investigational therapies recommended by an institutional MTB. White and Asian patients are less likely than Black/African American and Hispanic/Latino patients to be treated with MTB-recommended therapy, although these differences did not reach statistical significance. Further investigation of confounding variables including payor status and care fragmentation is necessary to clarify potential disparities and barriers to accessing innovative cancer care.
Prevalence of mismatch repair deficiency in a large prospective prostate cancer cohort.
Authors: Ciara S. McNevin, Mutaz Mohammed Nur, Cathal O'Brien, Brianan McGovern, Julia McFadden, Anne-Marie Baird, Karen Anne Cadoo, Martin P Barr, Steven G. Gray, Anna P. Keogh, Orla Sheils, Lesley Ann Sutton, Sinead Flanagan, Lorelei A Mucci, Konrad H. Stopsack, Stephen P. Finn
Journal: Journal of Clinical Oncology (2023)

5031 Background: Mismatch repair (MMR) deficiency and microsatellite instability (MSI) are predictive biomarkers for immunotherapy response. The best approach to identify patients with such tumors is unclear in prostate cancer. Methods: This study included men diagnosed with primary prostate cancer during prospective follow-up of the Health Professionals Follow-up Study (HPFS) and Physicians’ Health Study (PHS). The highest-grade/index lesions of tumor tissue from radical prostatectomy (95%) or transurethral resections of the prostate were mounted in triplicate on tissue microarrays. Immunohistochemistry for the MMR proteins MLH1, MSH2, MSH6, and PMS2 was performed, with scoring as MMR-deficient requiring a visible staining in a non-tumor internal positive control of the same case. For validation, a polymerase chain reaction-based MSI assay (Idylla MSI Test, Biocartis) was performed on tumor DNA of MMR-deficient cases and a selection of MMR-intact cases. Results: The study included 1016 men with prostate cancer. Tumor stage was predominantly pathologically localized (71% stage pT1/2, 18% T3a/b) with a full distribution of Gleason scores, including 20% Gleason score 6 (grade group 1), 36% 3+4 (grade group 2), 23% 4+3 (grade group 3), 8% 8 (grade group 4) and 13% 9-10 (grade group 5). MMR tumor scoring could be performed for MLH1 in 747 cases (75% of those with tumor tissue), for MSH2 in 903 cases (90%), for MSH6 in 708 cases (74%), and for PMS2 in 703 cases (72%). The remaining tumors were unevaluable due to lack of non-tumor tissue necessary as an internal positive control. Of the 903 tumors evaluable for MSH2 protein loss, 4 tumors had loss of MSH2 (prevalence 0.4%, 95% confidence interval [CI] 0.2–1.1%), and 3 of 708 evaluable tumors had concomitant loss of MSH6 (prevalence 0.4%, 95% CI 0.1–1.2%). No tumor had loss of MLH1 or PMS2. The MMR-deficient tumors had Gleason scores of 3+4, 8 (two cases), and 9–10. Tumor DNA of 1 of the 4 MMR-deficient tumors met the manufacturer’s cut-off for MSI-high; two additional MMR-deficient cases had non-zero repeats, with good reproducibility between tumor cores and technical replicates. One MSH2-deficient tumor and 6 DNA samples from 3 MMR-intact cases had repeat scores of zero. Conclusions: In this nationwide prospective study, MMR deficiency was rare in primary, surgically treated prostate cancer. This low prevalence contrasts with hospital-based studies of MMR deficiency and MSI that may have represented tumors with certain clinical features. The low prevalence and the need for an internal positive control for reliable scoring calls into question to what extent immunohistochemistry-based screening for MMR deficiency on limited tissue specimens, such as prostate biopsies, is routinely feasible.
Results from a phase (Ph) 1 clinical study of the all-oral regimen of CC-486 and venetoclax for acute myeloid leukemia (AML).
Authors: Maria Amaya, Christine McMahon, Jonathan Aaron Gutman, Brett Stevens, Connor Sohalski, Jennifer Tobin, Clayton Smith, Craig Jordan, Daniel Aaron Pollyea
Journal: Journal of Clinical Oncology (2023)

7034 Background: Venetoclax (Ven) with azacitidine (Aza) is the standard of care for newly diagnosed AML patients who are unfit for intensive induction chemotherapy. It is well known that this treatment also has activity in the relapsed and refractory (R/R) setting. However, this regimen requires seven consecutive daily SQ or IV doses of Aza each month. The relative inconvenience of this, and its negative impact on quality of life, may lead to its early discontinuation, possibly decreasing the overall efficacy of this regimen. An all-oral regimen may decrease infusion center visits, and potentially increase the efficacy of the regimen due to improved compliance. CC-486 is the oral formulation of Aza that is currently approved for post-induction chemotherapy maintenance in AML. Methods: This is a single center open label, Ph 1 study investigating CC-486 and Ven in R/R AML patients. In the dose escalation phase, subjects received CC-486 at one of two cohorts (200 mg PO days 1-14 and 300 mg PO days 1-14). Ven was given at the 400 mg/day PO regimen, for 28 days, after an initial intra-patient dose escalation per the standard of care. Using a 3+3 study design for the two cohorts, we aimed to determine the maximum tolerated dose (MTD) of CC-486 in combination with Ven. An expansion cohort is planned for 10 patients treated at the MTD. Results: As of February 1, 2023, 8 patients have been accrued. The average age at the time of enrollment was 64, and median prior treatment regimens was 1 (range 1-3). Four patients had received Ven in prior treatments. In cohort 1, there were no DLT events. There have been no DLT events in 5/6 patients enrolled in cohort 2. The most common hematologic toxicities were Gr 3-4 neutropenia (n = 7, 88%), Gr 3-4 anemia (n = 6, 75%), and Gr 3-4 thrombocytopenia (n = 4, 50%). The most common non-hematologic toxicities were Gr 1-2 nausea (n = 4, 50%), Gr 1-2 fatigue (n = 2, 25%), and Gr 1-2 diarrhea (n = 2, 25%). Best responses were complete remission (CR) (n = 2, 25%), partial remission (PR) (n = 1, 13%), and stable disease (SD) (n = 2, 25%). Three patients proceeded to an allogeneic stem cell transplant. Conclusions: CC-486 and Ven is an all-oral regimen being investigated for the treatment of R/R AML. Our Ph 1 dose escalation thus far has demonstrated a favorable safety profile for this regimen. Full Ph 1 findings and the MTD will be presented at the meeting. Responses have been seen in both dose cohorts, and patients have been bridged to hematopoietic stem cell transplant. Clinical trial information: NCT05287568 . [Table: see text]
Response monitoring with ctDNA in metastatic pancreatic cancer.
Authors: Jinwoo Ahn, Jin-Hyeok Hwang, Bomi Kim, Kwangrok Jung, Jaihwan Kim, Jong-chan Lee
Journal: Journal of Clinical Oncology (2023)

e16284 Background: Various studies about clinical usefulness of serial monitoring with liquid biopsy are being conducted actively in many types of cancer. However, there is not much in pancreatic cancer. We explored whether serial ctDNA monitoring in metastatic pancreatic cancer (MPC) can be beneficial for evaluating treatment response and predicting prognosis. Methods: A total of 51 MPC patients were prospectively enrolled. Blood samples were collected at every response evaluation until progression of disease (PD) or 5 th evaluation. Quantitative ctDNA were measured by droplet digital polymerase chain reaction using KRAS G12/G13 screening multiplex Kit (Bio-Rad) and reported as variant allele fraction (VAF). Percent change of ctDNA VAF (DctDNA(%) = (current VAF - previous VAF)/previous VAF*100) were correlated to radiographic responses by RECIST 1.1. Furthermore, Progression free survival (PFS) and overall survival (OS) were analyzed by DctDNA. Results: Among the 51 enrolled patients, baseline ctDNA were detected in 35 patients. During a median follow-up of 9.4 months, PD by radiographic response was observed in 24 patients. As expected, PD group showed higher DctDNA compared with non-PD group (p&lt;0.001). DctDNA for PD yielded Area Under Curve of 0.914 (p&lt;0.001) with 83.3% sensitivity at 90% specificity. Patients who showed early ctDNA clearance (undetectable level at first response evaluation) had longer PFS (8.1 m vs 4.7 m; HR 0.46; 95% CI 0.20 to 1.03; p=0.059) and OS (not reached vs 8.0 m; HR 0.20; 95% CI 0.06 to 0.74; p=0.009) than those who did not. In multivariable analysis, early ctDNA clearance was still associated with significantly longer PFS (HR 0.27; 95% CI 0.08 to 0.92, p=0.036) and OS (HR 0.08; 95% CI 0.02 to 0.54, p=0.007). Conclusions: Serial monitoring with ctDNA in MPC has considerable clinical potential in monitoring treatment response and predicting prognosis.
A prospective, cross-sectional, multicentre study to evaluate the clinical performance of the ColoSTAT in vitro diagnostic for the detection of biomarkers associated with colorectal cancer.
Authors: Emily He, Guy A. Van Hazel, Andrew Sloss, Stephen Pianko, Gregor Brown, Philip R. Clingan, Rajvinder Singh, Ann Solterbeck, Robert Traficante, Trevor Lockett, Louise Formby-Miller, Finlay Macrae
Journal: Journal of Clinical Oncology (2023)

3529 Background: Colorectal cancer (CRC) survival rates could be improved if more cancers were detected early. The ColoSTAT blood test and algorithm combines concentrations of 5 protein biomarkers with age and sex to provide an alternative to current CRC screening methods like the faecal immunochemical test (FIT). We compared the performance of ColoSTAT to colonoscopy in detecting CRC. Methods: Patients in this Australian study were either recently diagnosed with CRC using colonoscopy and progressing to surgery or neoadjuvant treatment (Cohort 1) or had no CRC history and were scheduled for colonoscopy (Cohort 2). Due to COVID-19 pandemic-related recruitment delays, the samples from Cohort 1 were supplemented with bio-banked blood samples (BBS) from patients with clinically confirmed CRC. Patients provided a 17 mL blood sample and were followed until start of cancer treatment or colonoscopy. All blood samples were de-identified prior to testing by an independent laboratory. The primary endpoints were ColoSTAT sensitivity of ≥73% (lower 95% confidence limit [LCL] &gt; 60%), and specificity ≥90% (LCL &gt; 80%). Sensitivity by TNM stage was an exploratory endpoint (ACTRN12619000301167). Results: Cohort 1 enrolled 29 patients, Cohort 2 enrolled 768 patients and 192 BBS were included. Patient demographic characteristics were similar in Cohorts 1, 2 and BBS. Overall, the median age of the patients (n = 989) was 64 years (range 40 to 88) and 53.4% were female. Definitive ColoSTAT results were obtained for 22 patients in Cohort 1, 554 in Cohort 2 and 81 in BBS. Overall, the estimated sensitivity of ColoSTAT for detection of CRC compared with colonoscopy was 81.3% (95%CL 73.0%-87.4%) and estimated specificity 91.0% (95%CL 87.7%-93.5%) (Table). Conclusions: The ColoSTAT test met the primary endpoints of performance based on sensitivity and specificity in detecting CRC compared to colonoscopy. ColoSTAT sensitivity and specificity for CRC were comparable with published performance parameters for FIT which range from 74-93% (sensitivity) and 85-96% (specificity). 1 Clinical trial information: ACTRN12619000301167 . Clinical trial information: ACTRN12619000301167 . [Table: see text]
Associations between early tumor shrinkage (ETS)/depth of response (DpR) and overall and post-progression survivals (OS/PPS) from the Analysis and Research in Cancers of the Digestive System (ARCAD) database.
Authors: Hideaki Bando, Yuriko Takeda, Toshihiro Misumi, Motoko Suzuki, Masashi Wakabayashi, Kentaro Yamazaki, Eiji Oki, Jean-Yves Douillard, Cornelis J. A. Punt, Miriam Koopman, Eric Van Cutsem, Carsten Bokemeyer, Alan P. Venook, Heinz-Josef Lenz, Yoshihiko Maehara, Thierry Andre, Qian Shi, Aimery De Gramont, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2023)

3566 Background: According to the various types of clinical trials for metastatic colorectal cancer (mCRC), ETS and DpR are suggested as the surrogates of OS. Whereas associations between ETS/DpR and OS/PPS in the era of chemotherapy (chemo) +anti-EGFR antibody (ab)/bevacizumab (bev) in 1st line therapy have not been elucidated. Methods: From 40,889 Individual patient data (IPD) from 59 studies in ARCAD mCRC database, 2,138 treatment-naïve pts with RAS wild-type (wt) mCRC were selected from 7 randomized studies (PRIME, CAIRO2, CRYSTAL, OPUS, CALGB80495, WJOG4407G, ATOM) of chemo with/without anti-EGFR ab or bev. The ETS was defined as 20%≥ tumor shrinkage at 8 ± 2wks (ETS+: ≥20%, ETS-: &lt;20%). Multivariate Cox regression models for OS/PPS were performed to investigate associations between ETS+ and ETS- by primary tumor location (overall/left-sided/right-sided), adjusting for potential confounders. DpR was defined as tumor shrinkage at nadir. OS/PPS were evaluated across quartile limits of DpR by multivariate Cox regression models. Results: In pts with overall or left-sided RAS wt mCRC, adjusted hazard ratios (HRs) of OS/PPS between ETS- and ETS+ for chemo +anti-EGFR ab, chemo +bev, and chemo alone showed great improvement, respectively (Table). In pts with overall or left-sided RAS wt mCRC, HRs of ETS for OS/PPS are higher in pts treated with chemo +anti-EGFR ab compared to those treated with chemo +bev or chemo alone. Compared to the pts with highest quartile (defined as ≥ 75th percentile (Q3)) of DpR, HRs of OS/PPS for lower quartile groups showed upward trends in pts with RAS wt &amp; overall (Table). Conclusions: ETS/DpR in pts with RAS wt mCRC might be a potential prognostic marker of OS/PPS regardless of targeted therapy and primary tumor location. Superior prognostic values of ETS+ are expected in pts treated with anti-EGFR ab. [Table: see text]
Nivolumab as second-line treatment of patients with metastatic renal cell carcinoma with high or normal fibrinogen levels: A prospective, cohort study.
Authors: Ilya Tsimafeyeu, Maria Volkova, Igor A. Utyashev, Ivan Gerk, Kristina Zakurdaeva
Journal: Journal of Clinical Oncology (2023)

e16510 Background: In a number of coagulation-related studies, elevated fibrinogen levels were found in patients with renal cell carcinoma (RCC) and correlated with more advanced disease. The impact of hyperfibrinogenemia on the clinical outcomes of immunotherapy remains uncertain. Methods: In this prospective cohort study, fibrinogen levels were measured one week prior to the second-line nivolumab therapy (240 mg or 480 mg every 2 or 4 weeks) and then monthly until disease progression or unacceptable toxicity. High fibrinogen level was defined as ≤5 g/L. Key eligibility criteria included metastatic clear cell RCC resistant to the first-line targeted therapy, ≤3 MSKCC risk factors, ECOG PS 0-2, platelet count &lt;400×10(9)/L, no heart diseases, no anticoagulation therapy, and age 40-65 years. The primary endpoint was overall survival (OS) in cohorts with high (H) and normal (N) fibrinogen levels. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and fibrinogen levels during therapy. Results: Between November 2018 and January 2021, 82 patients were enrolled, of whom 41 and 41, respectively, were recruited in H and N cohorts. The groups were well balanced at baseline. The median follow-up time was 32.4 months. Compared to patients in N cohort, patients in H cohort had shorter OS (P=0.001), shorter PFS (P&lt;0.01), and lower ORR (P=0.012). In H cohort, a below-median fibrinogen level was associated with longer observed OS (median, 23.7 vs. 19.4 months; P=0.03). In N cohort, 6 (15%) patients with stable disease had an increase in fibrinogen levels during nivolumab therapy. Patient characteristics and clinical outcomes are summarized. Conclusions: High fibrinogen levels affect the clinical outcomes in patients with metastatic renal cell carcinoma treated with second-line nivolumab. These findings require large-scale prospective validation. Clinical trial information: KCRB0181209 . [Table: see text]
Cancer of unknown primary with gastrointestinal profiles: A distinct CUP subset.
Authors: Aakash Tushar Shah, Jeannelyn Estrella, Priyadarsini Dasari, Anneleis Willett, Joelle Allam, Victoria Higbie, Phat Le, Michael Sangmin Lee, Aurelio Matamoros, Elizabeth A Lano, Kanwal Pratap Singh Raghav, Ryan W Huey
Journal: Journal of Clinical Oncology (2023)

3606 Background: Cancer of unknown primary (CUP) with a “gastrointestinal (GI) profile” appears to be a clinically distinct subset, based on immunophenotyping, specifically staining with cytokeratins 20 (CK20) and 7 (CK7), a type I and II keratin, respectively and caudal type homeobox 2 (CDX2) protein, a transcription factor expressed in nuclei of intestinal epithelial cells. However, only a limited clinicomolecular account of this entity exists. Comprehensive profiling is needed to substantially impact personalized therapeutics and improve prognosis. Methods: We identified 401 pts evaluated at MD Anderson Cancer Center. Pts were classified into 3 cohorts based on immunohistochemistry: lower GI profile CUP (LGI-CUP), other-GI profile CUP (OGI-CUP), or non-GI CUP (NGI-CUP). A control group of known lower GI primary cancers was derived from MSK-IMPACT data (cBioPortal, 1075 patients, LGI-KP). Clinical and pathological data including molecular profiling, therapy and survival were logged. Fisher-exact test was used. Kaplan-Meier method was used to estimate overall survival (OS) and compared with log-rank test. Results: Among 748 pts, 401 (53.6%) had adequate immunostaining for analysis. Of these, 72 (18.0%), 226 (56.4%) and 103 (25.7%) were classified as LGI-CUP, OGI-CUP, and NGI-CUP, respectively. LGI-CUP were enriched for adenocarcinoma (88% v 86% v 35%, P &lt; 0.0001) and good risk Culine score (59% v 51% v 37%, P = 0.02), compared to OGI-CUP and NGI-CUP, respectively. While NGI-CUP had greater proportions of poorly differentiated histology (91% v 55% vs 66%, P &lt; 0.0001) and bone metastases (30% vs 7% v 24%, P = 0.0001) compared to LGI-CUP and OGI-CUP, respectively. Comparison of key mutations is shown in table. Median OS of LGI-CUP (14.6 months [95%CI: 12.0 – 17.2]) was similar to OGI-CUP (14.3 months [95%CI: 10.7 – 18.0]) and NGI-CUP (16.2 months [95%CI: 12.4 – 20.0]), P = 0.75, but significantly lower than LGI-KP cohort (28.6 months, [95%CI 24.4 – 32.7], p &lt; 0.001). LGI-CUP was treated preferentially with fluoropyrimidine-based GI regimen [5-FU/capecitabine +/- oxaliplatin or irinotecan] (77% vs 43% v 5%) compared to OGI-CUP and NGI-CUP, respectively. However, median OS for LGI-CUP treated with 5-FU-based regimens was higher (16.0, 95%CI 13.0 – 19.0) than those treated with non-5-FU-based treatments (10.9, 95%CI 5.6 – 16.2), P = 0.002. Conclusions: LGI-CUP appears to be a molecularly distinct entity from and NGI-CUP, as well as lower GI CUP from known entities. LGI-CUP patients treated with 5-FU-based regimens appear to have improved survival. [Table: see text]